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Page 1: Properties of Biomaterials - Suranaree University of ...eng.sut.ac.th/ceramic/old/images_news/177.pdf · Properties of Biomaterials ... •Bioactive glass-ceramics. 21 ก ... Materials

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Properties of Biomaterials

426308 Ceramic Eng. Prop.

Asst. Prof. Dr. Sirirat T. Rattanachan

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Content (3 �������)

• Definition

• Application

• The responding of tissue to implants

• Biomaterials and design

• In vitro and In vivo

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Definitions

• A biomaterial is a nonviable material used in a medical device, intended to interact with biological systems. (Williams, 1987)

• Biocompatibility is the ability of a material to perform with an appropriate host response in a specific application. (Williams, 1987)

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Biomaterials market

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Applications

� ก����ก�������� ���� ก � (Skeletal systems)

���������ก��� ������ :Ti, Ti-Al-V

alloys, stainless steel, polyethylene

������ �������ก����ก : stainless

steel, Co-Cr alloys

�������ก����ก : Poly (methyl

methacrylate)

�������ก����ก: Hydroxyapatite

��������� �!�: Teflon, Dacron

��ก"#�� �!� : Ti, Al, calcium

phosphate

"#�� �!� : porcelain, zirconia

� ก����ก�������� ���� ก � (Skeletal systems)

���������ก��� ������ :Ti, Ti-Al-V

alloys, stainless steel, polyethylene

������ �������ก����ก : stainless

steel, Co-Cr alloys

�������ก����ก : Poly (methyl

methacrylate)

�������ก����ก: Hydroxyapatite

��������� �!�: Teflon, Dacron

��ก"#�� �!� : Ti, Al, calcium

phosphate

"#�� �!� : porcelain, zirconia Ref. 2

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� ����ก ����������������� (Cardiovascular systems)

���������: Dacron, Teflon, polyurethane

�$%� ��&'� �!�: stainless steel, carbon

�()ก�*�&�ก����+��������� : silicone rubber, Teflon, polyurethane

� ����ก ����������������� (Cardiovascular systems)

���������: Dacron, Teflon, polyurethane

�$%� ��&'� �!�: stainless steel, carbon

�()ก�*�&�ก����+��������� : silicone rubber, Teflon, polyurethane

Ref. 2

Applications

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� ���� (organs)

��� �����: Polyurethane

�������������:silicone-collagen composite

������: cellulose, polyacrylonitrile

ก������������� ���� !: silicone rubber

�� �������� (organs)(organs)

��� �����: Polyurethane

�������������:silicone-collagen composite

������: cellulose, polyacrylonitrile

ก������������� ���� !: silicone rubber

Applications

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� ������������ก������� (Senses)

ก����ก ���%�&� (Cochlear): Platinum electrode

�������� �!� (Intraocular lens): poly(methylmethacrylate), silicone rubber, hydrogel

,��� ,�� ����� (contact lens):silicone-acrylate, hydrogel

�����ก���� ก��'ก�� (Corneal bandage): collagen, hydrogel

� ������������ก������� (Senses)

ก����ก ���%�&� (Cochlear): Platinum electrode

�������� �!� (Intraocular lens): poly(methylmethacrylate), silicone rubber, hydrogel

,��� ,�� ����� (contact lens):silicone-acrylate, hydrogel

�����ก���� ก��'ก�� (Corneal bandage): collagen, hydrogel

Ref. 2

Applications

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Tissue Response to Implants

• Interactions between implant surface and tissue

implant

waterDissolved ions

Free bimolecular

Chemotaxis ก����������� ��������ก�����

Phagocytosis ��ก��ก�����������������ก���

Macrophage activation ������������������ �ก��������ก���

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Chemotaxis

Target

Macrophages

Macrophages activation

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The response of hard tissue to implantation

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Scheme of process of wound healing in a simple incisional wound

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Scheme of process of wound healing in the presence of a foreign body

�������!"���"�"�

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Sequence of surface reaction in the bioactive bonding to bone

Bioactive glass (SiO2-CaO-Na2O)Bioactive glass (SiO2-CaO-Na2O)

�ก�"# $� SiOH bond

Polycondensation of SiOH+SiOH�Si-O-Si

Adsorption of amorphous Ca+PO4+CO3

Crystallization of Hydroxyl carbonate apatite (HCA)

Adsorption of biological moities in HCA layerAction of macrophagesAttachment of stem cells

Differentiation of stem cells ���!��������%���&������'#�����Generation of matrix

Crystallization of matrix

deve

lopm

ent

Bone growth

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Factors affecting implant-tissue interfacial response

• (�" �� �"�)*�+

•�,� �� �"�)*�+

•�,����-��� �- �

•.�����������-��� �- �

•����#�����-��

• �/�ก���������������-��

• ก���(����% ก�������

•��������ก�����

•(�" ���0����

• �������1�2� ���0����

• ��� ���0����

•��������������"+��0����

•��������������"���-��� �- �

• ก�������3������ก�" 40���-��� �- �

• ก���(����%�����

• ��������ก�����

Implant sideTissue side

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Various methods of prosthesis fixation

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Bioceramics• Alumina• Zirconia• Calcium phosphate• Hydroxyapatite• Bioactive glasses• Bioactive glass-ceramics

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�������ก���ก����ก

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Bone tissue

• Schematic drawings of bone tissue. On the left is a depiction of the 3 types of lamellar bone in the shaft of a long bone. The Haversian systems, and inner and outer lamella are shown. On the right, is a higher magnification diagram of a Haversian canal and contiguous lamella. Taken from Junqueira and Carneiro, Basic Histology, a text and atlas, pp. 44 and 46, Figures 8-6 and 8-8.

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Physical properties of materials used for joint prosthesis and bone

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(�" �� �"����ก�������%��0����

• � �"���&#�5 � ��0���������2��� �"����

• � �"�3�%��&#�5����6� Bioinert � �ก�" Fibrous tissue

• � �"�3�%��&#�5����6� Bioactive � �ก�"ก���(����%ก ���0����

• � �"�3�%��&#�5����6� Biodegradable � ��ก���������������"�����0�������$���(���3"�

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Types of Tissue attachment of bioceramic prostheses

Tricalcium phosphate

Bioactive glasses

Replacement with tissueResorbable

Bioactive glasses, Bioactive glass-ceramics HA

Interfacial bonding with tissues (bioactive fixation)

Bioactive

Hydroxyapatite (HA),

HA coated porous metals

Ingrowth of tissues into pores

(biological fixation)

Porous

Al2O3, ZirconiaMechanical interlock

(morphological fixation)

Nearly inert

ExampleType of attachmentType of implant

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Bioinert

����� ���&� �"�)*�+ ��.#ก����� ���,*�����

�"����������ก �.������#�������� ����%ก���4ก��"���ก

• Alumina

• Zirconia ��& Y-TZP, Mg-PSZ

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Alumina for surgical implants

• High density, purity (>99.5% Al2O3) is used in load-bearing hip protheses and dental implants – Excellent corrosion resistance

– Good compatibility

– High wear resistance

– High strength

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Use of zirconia in surgical implants

• Tetragonal zirconia stabilized with yttria (TZP)

• Magnesium oxide partially stabilized zirconia (MG-PCZ)

• High fracture toughness

• High flexural strength

• Lower young’s modulus

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Bioactive glass

• Bioglass® 45S5: 45%SiO2, 24.5 Na2O, 24.4% CaO and 6%P2O5� melt at 1300-1450ºC

• Na2O-CaO-SiO2 glass ����"��� P2O5, B2O3 ��� CaF2• Their rapid rate of surface reaction� leads to fast tissue bonding

• Mechanical weakness and low fracture toughness

• Application: middle ear device

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Bioactive glass-ceramics

• Apatite-wollastonite (A/W) glass ceramics: 3CaO.P2O5-CaO.SiO2-

MgO.CaO.2SiO2� fine grained

oxyapatite and fibrous β-wollastoniteprecipitated.

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Mechineable and phosphate glass-ceramics

• BIOVERIT I and BIOVERIT II: a mica-apatite glass-ceramics (SiO2-(Al2O3)-MgO-Na2O-K2O-F-CaO-P2O5 base glass system.

• Clinical applications: Orthopaedic surgery (spacers), head and neck surgery (middle ear implants), stomatology (tooth root and veneer laminates)

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Calcium phosphate ceramics

• ������ก���������� ��ก 3"�"�ก �ก��"1ก���,*��5��

• ��������ก�����������ก���� ."���� "�%� Ca/P = 0.5 -2.0

• Dicalcium phosphate dihydrate (DCPD) or Brushite �

CaHPO4.2H2O (Ca/P = 1.0)

• Dicalcium phosphate (montite) CaHPO4

• Tricalcium phosphate (Ca3(PO4)2) Ca/P = 1.5

• Tetracalcium phosphate (Ca4O(PO4)2) Ca/P = 2.0

• Hydroxyapatite Ca/P = 1.67

• Octacalcium phosphate (Ca8H2(PO4)6.5H2O)

Ca/P = 1.33

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Apatite

Hydroxyapatite (Ca10(PO4)6(OH)2)

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Forms and application

• Dense hydroxyapatite

• Porous hydroxyapatite

• Coating

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Synthetic hydroxyapatite

Ca10(PO4)6(OH)2 or HA

(Ca,X)10(PO4,HPO4,CO3)6(OH,Y)2X= Mg, Na, Sr = cation

Y = choride or fluoride = anion

Sintered HA

Porous sHA

• �������� ����� ��ก calcium nitrate,

Diammonium hydrogen phosphate

And NH4OH • ก����ก��� ���� ��ก���� �����ก��

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��� �� ����� ���!����ก"��#�$

• ��� �����ก� 3"��ก% bending strength, flexure testing, Fracture toughness, hardness

• ��� �����-�� 3"��ก% surface charge, hydrophilicity or hydrophobicity� surface analysis and solution

analysis

• ��� ��"������� ��ก 3"�ก ��%��ก�� Bioactive and Biocompatability

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Bioactivity and biocompatibility

• Bioactivity: ���ก���"����� in vivo – 74ก5� ���ก���(����% �ก��"1กก �� �"�)*�+ ����� !�����������

��8���+ก���4"�ก��ก �ก��"1ก– � ��%�� Bioactive glass �� 42-53 %SiO2 �4�����(����%

ก �ก��"1ก3"�6��+ 1 � �%� Bioactive glass ����� 54-60%SiO2 ���(����%ก �ก��"1ก3"�6��+ 2 � �"���

– ก��74ก5�#A��ก��� �� �"������(%+�������������ก�������� pH (7.2-7.4) �����ก � �����+�%��ก����5��

– Bioactive glass +�������� SBF ."�ก��"1"� �.������ก �������������( 0.�����������-�� �(%�ก�" HCA

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• Biocompatibility: ��"���"#�"�$����$ก�%��$!&'(� � ���ก�!ก���%$������"#�"����)��%*��$!&'(� ���#� – In vitro � +�ก���!$%ก���%$��������, ������$����-.�%.&��!/ ���� +�

ก���!$%�%"#��/�ก�������ก��01ก2� �$���������� �!ก����%����������,�������������$�%)�3, ก��1!�ก��������,%�4"#������$!&�1#�)�ก�%.���� +���1ก���.������%�������$!&

– In vivo �!$% �$���������� $���,�!�����!��5ก�����ก�%ก��01ก2�ก������ก��!)ก������ก $���$���, �6��������ก�%ก��01ก2�ก������ก��!)ก���ก��$�/��ก��!)ก�1#� ���

– Histomorphometry � +�ก��01ก2� ����3��ก��!)ก����ก�!�1#� ������������7� ���$!&'(� �

Bioactivity and biocompatibility

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Consequences of Implant-Tissue interaction

Tissue replaces implantDissolution of implant

Tissue forms an interfacial bond with the implant

Bioactive

Tissue forms a non-adherent fibrous capsule around the implant

Biologically nearly inert

Tissue diesToxic

ConsequenceImplant-tissue reaction

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Biodegradable

'(�-ก���+��+ก����ก

����(���(� ��� scaffold = cell + biomaterials

Inorganic compounds: HA, bioactive glass

Biopolymers: PMMA, PE

Biodegradable polymer: aliphatic polyesters=

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Bioactive polymer/ceramic composite scaffold

Bioactive ceramic phase

(bioglass©, HA)

Biodegradable and bioactive composites

Biodegradable polymer

(PDLLA, PHA, PLGA, collagen)

Bioactive phase

as filler or coating

Dense compositesPorous composites

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Tissue engineering

scaffold

����-��$ �+ก����+��+��!+�

.�& ���������ก�� �$��'.��������)���!��)/������ก����ก���!�������0���)/�$1

0�� .�& ��ก$�ก����ก��- ����ก��0����ก�-���+ก�!

��-& ���������ก�������2�3%���)�-- ����-����0��

ก����-���+����������

ก��& ��ก$�ก������+���%��!���������������4�!&�

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In Vitro Testing of Cytotoxicity of Materials

• Cellular mechanisms of toxicity can be described using biochemical assays

• Valid alternatives to animal models are needed.

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ก�����0��������� �"�� ��%���!���%&� Osteoblasts ���'���!���(& alpha minimum essential medium

Scaffold ���(&��&%���)���ก*��+(& culture medium 3 h, 37oC

5%CO2 and 95% air

�!�����,���'������&-���� scaffold �.�&�&��,)&�&�&����,�& medium ��ก/ 2 ��&

�+�� ��!���)��&��.�&�&�!�����,�ก�� = �.�&�&�!������,� +& – �.�&�&�!�����,�+����ก�� 2��("+ hemacytometer

ก�� ��� �ก���$�,��.�&�& �.���+2��("+ fluorescence #��( +ก���+�� �

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Indirect contact (In vitro testing)

Reagent control Negative control

Positive control Sample

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Direct contact

Reagent control Negative control

Positive controlSample

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Standards for testing cytotoxicity

• ISO technical committee (international)

• CEN technical committee (European)

• ISO 10993

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In vivo����ก����� ���+ ��$� ��!( �5

������ 6#+����(

���%!+�)/���!����� 2-4 ��)�� �

��������ก�� ���+�����! SEM, TEM

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SEM micrographs (a and c) and toluidine blue-stained (b and d) thin sections (after glass removal and re-embedding) of H (a and b) and HZ5 (c and d) flat specimens implanted into calvaria for 30 days. (a) Several boneremnants, most showing erosion surfaces (indented contours). (b) A great (multinucleated) osteoclast (arrow)eroding the bone beneath of the glass (H). (c) New bone (arrow) formed in apposition to the bone spared byosteoclasts; note also that much bone has been resorbed (below and on the left of the arrow). (d) Active osteoblasts(arrows) forming new bone in apposition to the pre-existing bone inside the fibrous tissue separating the bone fromthe HZ5 glass

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Bioceramics

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Form, phase and function of bioceramics

Replacement and augmentation of tissue,

Replace functioning parts

Single crystal

Polycrystalline

Glass

Glass-ceramic

Composite (multi-phase)

Bulk

Tissue bonding,

corrosion protection

Polycrystalline

Glass

Glass-Ceramic

Coating

Space-filling, therapeutic treatment,

Regeneration of tissues

Polycrystalline

Glass

Powder

FunctionPhaseForm

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Any questions?